110,712 research outputs found

    What Is the Integrated Information Theory of Consciousness?

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    In the first instance, IIT is formulated as a theory of the physical basis of the 'degree' or ‘level’ or ‘amount’ of consciousness in a system. In addition, integrated information theorists have tried to provide a systematic theory of how physical states determine the specific qualitative contents of episodes of consciousness: for instance, an experience as of a red and round thing rather than a green and square thing. I raise a series of questions about the central explanatory target, the 'degree' or ‘level’ or ‘amount’ of consciousness. I suggest it is not at all clear what scientists and philosophers are talking about when they talk about consciousness as gradable. I also raise some questions about the explanation of qualitative content

    Seeing the Forest for the Trees: Using the Gene Ontology to Restructure Hierarchical Clustering

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    Motivation: There is a growing interest in improving the cluster analysis of expression data by incorporating into it prior knowledge, such as the Gene Ontology (GO) annotations of genes, in order to improve the biological relevance of the clusters that are subjected to subsequent scrutiny. The structure of the GO is another source of background knowledge that can be exploited through the use of semantic similarity. Results: We propose here a novel algorithm that integrates semantic similarities (derived from the ontology structure) into the procedure of deriving clusters from the dendrogram constructed during expression-based hierarchical clustering. Our approach can handle the multiple annotations, from different levels of the GO hierarchy, which most genes have. Moreover, it treats annotated and unannotated genes in a uniform manner. Consequently, the clusters obtained by our algorithm are characterized by significantly enriched annotations. In both cross-validation tests and when using an external index such as protein–protein interactions, our algorithm performs better than previous approaches. When applied to human cancer expression data, our algorithm identifies, among others, clusters of genes related to immune response and glucose metabolism. These clusters are also supported by protein–protein interaction data. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online.Lynne and William Frankel Center for Computer Science; Paul Ivanier center for robotics research and production; National Institutes of Health (R01 HG003367-01A1

    A distributional model of semantic context effects in lexical processinga

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    One of the most robust findings of experimental psycholinguistics is that the context in which a word is presented influences the effort involved in processing that word. We present a novel model of contextual facilitation based on word co-occurrence prob ability distributions, and empirically validate the model through simulation of three representative types of context manipulation: single word priming, multiple-priming and contextual constraint. In our simulations the effects of semantic context are mod eled using general-purpose techniques and representations from multivariate statistics, augmented with simple assumptions reflecting the inherently incremental nature of speech understanding. The contribution of our study is to show that special-purpose m echanisms are not necessary in order to capture the general pattern of the experimental results, and that a range of semantic context effects can be subsumed under the same principled account.›

    Profound effect of profiling platform and normalization strategy on detection of differentially expressed microRNAs

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    Adequate normalization minimizes the effects of systematic technical variations and is a prerequisite for getting meaningful biological changes. However, there is inconsistency about miRNA normalization performances and recommendations. Thus, we investigated the impact of seven different normalization methods (reference gene index, global geometric mean, quantile, invariant selection, loess, loessM, and generalized procrustes analysis) on intra- and inter-platform performance of two distinct and commonly used miRNA profiling platforms. We included data from miRNA profiling analyses derived from a hybridization-based platform (Agilent Technologies) and an RT-qPCR platform (Applied Biosystems). Furthermore, we validated a subset of miRNAs by individual RT-qPCR assays. Our analyses incorporated data from the effect of differentiation and tumor necrosis factor alpha treatment on primary human skeletal muscle cells and a murine skeletal muscle cell line. Distinct normalization methods differed in their impact on (i) standard deviations, (ii) the area under the receiver operating characteristic (ROC) curve, (iii) the similarity of differential expression. Loess, loessM, and quantile analysis were most effective in minimizing standard deviations on the Agilent and TLDA platform. Moreover, loess, loessM, invariant selection and generalized procrustes analysis increased the area under the ROC curve, a measure for the statistical performance of a test. The Jaccard index revealed that inter-platform concordance of differential expression tended to be increased by loess, loessM, quantile, and GPA normalization of AGL and TLDA data as well as RGI normalization of TLDA data. We recommend the application of loess, or loessM, and GPA normalization for miRNA Agilent arrays and qPCR cards as these normalization approaches showed to (i) effectively reduce standard deviations, (ii) increase sensitivity and accuracy of differential miRNA expression detection as well as (iii) increase inter-platform concordance. Results showed the successful adoption of loessM and generalized procrustes analysis to one-color miRNA profiling experiments
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